糖尿病患者Apo－Al、Apo－B测定及其临床意义

本文对６０例糖尿病患者及６２例正常人的血清载脂蛋白（Ａｐｏ）－Ａｌ，Ａｐｏ－Ｂ高密度脂蛋白（ＨＤＬ）和低密度脂蛋白（ＬＤＬ）水平进行了测定，结果显示：（１）糖尿病患者Ａｐｏ－Ａｌ水平和Ａｐｏ－Ｂ水平均明显高于正常人（Ｐ＜０．０１）。（２）住院治疗前，糖尿病患者血清ＨＤＬ水平明显低于正常人（Ｐ＜０．０１）。（３）住院治疗期间糖尿病患者血清ＨＤＬ水平显著增高（Ｐ＜０．０１），而ＬＤＬ水平无明显改变（Ｐ＞０．０５）。     

载脂蛋白A多态性在老年冠心病中检测的临床意义

目的探讨老年冠心病（ＣＨＤ）和健康老年人载脂蛋白Ａ（ＡｐｏＡ）异构体多态性表型、脂蛋白（ａ）［Ｌｐ（ａ）］及血脂水平的临床关系。方法检测１０４例老年ＣＨＤ患者（陈旧性心肌梗塞３１例，稳定型心绞痛３８例，心律失常型２０例，心力衰竭型１５例）血清ＡｐｏＡ异构体多态性表型和血清Ｌｐ（ａ）及血脂水平，并与６８例健康老年人对照分析。结果ＣＨＤ组Ｌｐ（ａ）和血脂水平明显高于对照组（Ｐ＜０．０５或Ｐ＜０．０１）。ＣＨＤ组ＡｐｏＡ表型检出率为８２．７％，对照组为７５％。ＡｐｏＡ表型频率分布与ＡｐｏＡ表型分子量呈非常显著正相关（ＣＨＤ组ｒ＝０．９９２７，对照组ｒ＝０．９６９７，Ｐ＜０．０１）。结论ＡｐｏＡ多态性表型在临床上比Ｌｐ（ａ）及血清脂质更具有参考价值。     

老年冠心病病人血清脂质水平研究

测定１０２例老年冠心病病人血清ＴＣ、ＴＧ、ＨＤＬ－Ｃ、ＡｐｏＡ１和ＡｐｏＢ含量并计算ＡｐｏＡ１和ＡｐｏＢ的比值，与１００例健康人进行比较。结果表明：冠心病病人ＡｐｏＢ明显高于对照组（Ｐ＜０．０１），ＡｐｏＡ１／ＡｐｏＢ低于对照组（Ｐ＜０．０５）。９１．２％男性病人和７８．９％女性病人ＡｐｏＡ１／ＡｐｏＢ低于对照组，男女之间下降比例有差异，提示ＡｐｏＡ１／ＡｐｏＢ比值下降同样是老年冠心病病人的危险因素     

2型糖尿病患者脂质代谢改变的临床意义

对２７６例２例糖尿病（ＮＩＤＤＭ）患者的甘油三酯（ＴＧ）,总胆固醇（ＴＣ）,载脂蛋白Ａ１和Ｂ（ＡｐｏＡ１,ＡｐｏＢ）,高密度脂蛋白（ＨＤＬ）,低密度脂蛋白（ＬＤＬ）脂蛋白（ａ）（Ｌｐ（ａ）进行了检测,并与１８９例正常人（对照组）作对照,结果ＮＩＤＤＭ组ＴＧ,ＴＣ,ＡｐｏＢ,ＬＤＬ,Ｌｐ（ａ）,明显高于对照组（Ｐ〈０．０１）,ＨＤＬ明显低于对照组（Ｐ〈０．０１）,两组ＡｐｏＡ１无显著差异（Ｐ〉０．０     

病毒性肝炎和肝硬化患者IL－6、TNF－α的变化

为研究白细胞介素－６（ＩＬ－６）、肿瘤坏死因子（ＴＮＦ－α）在肝炎和肝硬化（ＬＣ）患者中的作用。检测了１５例正常人，１８例急性病毒性肝炎（ＡＨ），３７例慢性肝炎（ＣＨ），２０例ＬＣ患者血清及外周血单个核细胞（ＰＢＭＣ）的ＩＬ－６、ＴＮＦ－α水平。结果以ＣＨ患者ＩＬ－６、ＴＮＦ－α水平最高（血清及ＰＢＭＣ的ＩＬ－６水平分别为７２．１±３２．９４Ｕ／ｍｌ，１４０．７±３３．５Ｕ／ｍｌ；血清及ＰＢＭＣ的ＴＮＦ－α水平为３．９７±１．３８ｎｇ／ｍｌ，６．３５±１．４１ｎｇ／ｍｌ）。恢复期或稳定期ＴＮＦ－α和ＩＬ－６水平明显低于急性期或活动期（Ｐ＜０．０１）。ＣＨ患者肝组织学活动指数（ＨＡＩ）分数与ＰＢＭＣＩＬ－６和ＴＮＦ－α水平呈正相关（γ分别为０．８９，０．６８；Ｐ＜０．０５）。提示ＩＬ－６和ＴＮＦ－α是肝脏损害重要的炎症介质，介导肝细胞损害。     

高血压病患者血清脂蛋白、载脂蛋白异常与胰岛素抵抗的关系

目的：探讨高血压病患者血脂／载脂蛋白异常与胰岛素抵抗的关系。方法：以空腹胰岛素／空腹葡萄糖比值和口服葡萄糖负荷后胰岛素曲线下面积／葡萄糖曲线下面积比值作为胰岛素抵抗指标，与空腹血脂／载脂蛋白进行直线相关分析。结果：与正常对照组（ｎ＝２１）比较，高血压病组（ｎ＝３２）血清甘油三酯（ＴＧ）、低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）、载脂蛋白（Ａｐｏ）Ｂ、空腹胰岛素、空腹胰岛素／空腹葡萄糖比值以及胰岛素曲线下面积、葡萄糖曲线下面积和胰岛素曲线下面积／葡萄糖曲线下面积比值均显著增加（Ｐ＜０．０５～０．００１），高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）、ＨＤＬ２－Ｃ、ＡｐｏＡＩ及ＡｐｏＡＩ／ＡｐｏＢ比值均显著降低（Ｐ＜０．０５～０．００１）。高血压病组空腹胰岛素／空腹葡萄糖比值和胰岛素曲线下面积／葡萄糖曲线下面积比值均分别与甘油三酯、低密度脂蛋白胆固醇和ＡｐｏＢ呈正相关（Ｐ＜０．０５～０．０１），与ＨＤＬ２－Ｃ、ＡｐｏＡＩ和ＡｐｏＡＩ／ＡｐｏＢ比值呈负相关（Ｐ＜０．０５～０．００１）。正常对照组上述指标间则无相关（Ｐ＞０．０５）。结论：高血压病患者血脂／载脂蛋白异常与胰岛素抵抗密切相关。     

老年痴呆患者apoE基因型分布

目的观察中国老年痴呆患者ａｐｏＥ基因型的分布，初步探讨ａｐｏＥ在老年痴呆发病中的作用。方法应用聚合酶链式反应（ＰＣＲ）对３５例健康人、２３例多梗塞性痴呆（ＭＩＤ）及１７例老年性痴呆（ＡＤ）患者进行ａｐｏＥ基因多态性分析，测定血清胆固醇（ＴＣ）、甘油三酯（ＴＧ）、高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）、低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）、载脂蛋白ＡⅠ（ａｐｏＡⅠ）、载脂蛋白Ｂ（ａｐｏＢ）和载脂蛋白Ｅ（ａｐｏＥ）的浓度。结果ＡＤ组与健康对照组在ａｐｏＥ基因频率及等位基因频率分布上的差异有显著性（χ２＝１１．５，Ｐ＜０．０５；χ２＝１６．２，Ｐ＜０．０１）；ＭＩＤ组与健康对照组间差异无显著性（Ｐ＞０．０５）；应用Ｗｏｏｌｆ公式计算，发现ａｐｏＥε４等位基因与ＡＤ之间有显著性关联（χ２＝７．７，Ｐ＜０．０１），相关危险度（ＲＲ）＝３．０。ＡＤ组血清ａｐｏＥ水平显著高于对照组（Ｐ＜０．０５），而ＴＣ、ＬＤＬ－Ｃ、ａｐｏＡⅠ、ａｐｏＢ显著低于对照组（Ｐ＜０．０５）。结论结果提示ａｐｏＥε４等位基因与老年性痴呆有显著性关联，ａｐｏＥε４可能是ＡＤ发病的危险因素。     

中老年人高密度脂蛋白胆固醇与性激素的关系

对１０２例年龄≥４５岁的中老年非糖尿病人群的高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）载脂蛋白Ａ１（ＡｐｏＡ１）进行测定，并观察它们与性激素的关系。经逐步回归分析，结果显示了ＨＤｌ－Ｃ与年龄、体重指数（ＢＭＩ）、空腹血浆胰岛素（Ｆ－Ｉｎｓ）水平显著负相关，与雌二醇／睾丸酮（Ｅ２／Ｔ）比值呈显著正相关（Ｐ＝０．０００１），与Ｔ呈显著负相关（Ｐ＝０．０００１）。在调整年龄、ＢＭＩ和ＩＮＳ、Ｆ后，Ｅ２／Ｔ比值是影响ＨＤＬ－Ｃ水平的独立因素。ＡｐｏＡ１，作为因变量进行相同的分析得到了与ＨＤＬ－Ｃ相似的结果。     

老年男性冠心病患者血清硫酸脱氢表雄酮含量变化的临床意义

目的观察老年男性冠心病患者血清硫酸脱氢表雄酮（ＤＨＥＡ－Ｓ）含量变化，探讨其与睾酮（Ｔ）、胰岛素（ＩＮＳ）、血糖（Ｇｌｕ）、甘油三酯（ＴＧ）、总胆固醇（ＴＣ）、载脂蛋白Ｂ（ａｐｏＢ）及年龄的相关性。方法用放免法测定６９例老年男性冠心病患者血清ＤＨＥＡ－Ｓ含量，并与３５例年龄匹配的男性健康人对照。结果冠心病组ＤＨＥＡ－Ｓ含量（２．９６±１．８０μｍｏｌ／Ｌ）显著低于对照组（４．０６±１．７６μｍｏｌ／Ｌ，Ｐ＜０．０１），病情重组（２．４４±１．３６μｍｏｌ／Ｌ）又明显低于病情轻组（３．３２±２．１２μｍｏｌ／Ｌ，Ｐ＜０．０５）；冠心病组ＤＨＥＡ－Ｓ含量与年龄呈负相关（ｒ＝－０．３０５４，Ｐ＜０．０１），对照组两者也呈负相关（ｒ＝－０．３６１５，Ｐ＜０．０５）；冠心病患者ＤＨＥＡ－Ｓ降低与空腹血清ＩＮＳ、ＴＧ及ａｐｏＢ增高均呈负相关（分别为ｒ＝－０．３２９７、－０．２５１９及－０．２４１３，Ｐ＜０．０１或０．０５）。结论老年男性冠心病患者血清ＤＨＥＡ－Ｓ含量降低，并与冠心病某些危险因素如老年、高胰岛素血症、高甘油三酯血症、血清ａｐｏＢ高值相关，但其确切的发病机理有待深入研究。     

肥胖型糖尿病并脂肪肝患者血清载脂蛋白B水平的临床观察

血清载脂蛋白Ｂ（ＡＰＯ－Ｂ）含量增高，是在糖尿病糖代谢障碍基础上脂代谢异常的早期判断指标之一。肥胖是发生糖尿病，脂肪肝的重要因素。本文对５８例糖尿病患者测定了血ＡＰＯ－Ｂ含量和肝脏Ｂ超显像观察，结果发现血脂尚正常时糖尿病ＡＰＯ－Ｂ值不仅高于正常对照组（Ｐ＜０．０１），而且高于冠心病组。其中３２例肥胖型中有２６例并脂肪肝（１６例经ＣＴ证实），其ＡＰＯ－Ｂ水平及合并大血管、微血管病变发生率明显高于非肥胖型（Ｐ＜０．０１）：血液粘度增高、血液流态、流速改变等程度，亦以肥胖型更严重。     

冠心病患者氧化低密度脂蛋白与微量元素水平的关系

目的：探讨冠心病患者机体微量元素代谢改变与氧化低密度脂蛋白之间的关系。方法：测定６０例冠心病患者（冠心病组）及３６例正常人（正常对照组）的血浆氧化低密度脂蛋白（ＯＸＬＤＬ）和血清锌、硒、铜等１３种元素及血清铜蓝蛋白（ＣＰ）、铁蛋白（ＳＦ）、脂质、脂蛋白水平，各检测指标与ＯＸＬＤＬ行直线相关分析及多因素逐步回归分析。结果：冠心病组血浆ＯＸＬＤＬ、血清甘油三酯（ＴＧ）、低密度脂蛋白、铜、铜蓝蛋白、铁蛋白、铜／锌水平显著高于正常对照组，血清硒、锌、高密度脂蛋白（ＨＤＬＣ）、铬水平显著低于正常对照组。直线相关分析表明甘油三酯、铜、铜蓝蛋白、铜／锌与ＯＸＬＤＬ呈显著正相关，而ＨＤＬＣ、硒、锌与ＯＸＬＤＬ呈显著负相关。多因素逐步回归分析表明硒、锌、铜、铁可影响低密度脂蛋白的氧化。结论：铁、铜可能促进ＯＸＬＤＬ的形成，硒、锌对低密度脂蛋白的氧化可能起保护作用     

Effects of nicotinic acid on serum cholesterol concentrations of high density lipoprotein subfractions HDL2 and HDL3 in hyperlipoproteinaemia

Nicotinic acid was given in a 4-g daily dose for 6 weeks to 41 weight-stable patients of mean age (+/- SD) 52 +/- 9 years, with type IIa, type IIb or type IV hyperlipoproteinaemia (HLP), in order to study its effects on serum cholesterol concentrations of high density lipoprotein (HDL) subfractions HDL2 and HDL3. The triglyceride and cholesterol levels of serum very low density (VLDL) and low density (LDL) lipoproteins decreased during treatment (P less than 0.001). Serum HDL and HDL2 cholesterol levels increased by 37% and 135%, respectively. These changes were positively correlated (r = 0.93; P less than 0.001). There was no significant change in mean serum HDL3 cholesterol concentration. A negative correlation existed between changes in HDL3 and HDL2 cholesterol levels (r = -0.54; P less than 0.001). Multiple stepwise linear regression analyses revealed that the initial HDL3 cholesterol predicted more than 30% of the increase in HDL2 cholesterol. Changes in the concentrations of HDL2 and HDL3 cholesterol after 6 weeks of drug treatment were not related to the type of HLP, neither were these effects of nicotinic acid correlated with changes in VLDL or LDL lipid levels. The concept has previously been proposed, on the basis of in vitro data, that HDL2 is formed from HDL3 particles in the blood. Our results suggest that, in man, this reaction is stimulated in vivo by prolonged nicotinic acid therapy.     

Susceptibility of low- and high-density lipoproteins from diabetic subjects to in vitro oxidative modification.

AIMS: To investigate the hypothesis that lipid peroxidation of both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) is important in the development of atherosclerosis. METHODS: We have investigated whether LDL and HDL from patients with Type 1 diabetes mellitus (DM, n = 16) and Type 2 DM (n = 15) is more susceptible to Cu2+ -induced lipid peroxidation than LDL and HDL from a similar number of nondiabetic controls matched for age, gender and serum cholesterol. RESULTS: The vitamin E content of LDL and HDL from both groups of diabetic patients was not significantly different from controls. The LDL from Type 2 diabetic patients and HDL from both diabetic groups were significantly richer in triglyceride than controls. Phospholipid was decreased in LDL from Type 2 diabetic patients and protein was decreased in HDL in Type 1 DM, but otherwise the composition of LDL and HDL in diabetic subjects was similar to controls. No significant differences were observed in the generation of conjugated dienes or lipid peroxides in either LDL or HDL when the two groups were compared with each other or with their respective controls. CONCLUSIONS: Increased lipid peroxidation occurring in vivo in diabetes is unlikely to be the result of increased susceptibility of lipoproteins to lipid peroxidation, but rather to increased generation of free radicals, to oxidation of lipids other than those present in serum lipoproteins or to decreases in antioxidant systems other than the fat-soluble antioxidants present in lipoproteins.     

Hypertriglyceridaemia and its influence on low density lipoprotein regulation of cellular cholesterol synthesis: a comparison between hypertriglyceridaemic diabetic and non-diabetic patients.

The present investigation was undertaken to examine the relationship between serum triglyceride and composition of lipoprotein. Six groups of patients were examined, three with Type 2 (non-insulin-dependent) diabetes and three without diabetes. The groups were further categorized on the basis of their serum cholesterol and triglyceride levels into normocholesterolaemic (serum cholesterol less than 6.5 mmol l-1) and hypercholesterolaemic (serum cholesterol greater than 6.5 mmol l-1) with and without hypertriglyceridaemia (serum triglyceride greater than or less than 3.5 mmol l-1). Low density lipoprotein (LDL) composition was determined and regulation of cholesterol synthesis by LDL was assessed by measuring its effect on [14C]-acetate incorporation into mononuclear leucocyte cholesterol. LDL from the hypercholesterolaemic diabetic patients had a significantly higher esterified cholesterol content when the patients were normotriglyceridaemic (1.14 +/- 0.04 vs 0.76 +/- 0.04 g g-1; p less than 0.01). The ability of LDL to suppress cholesterol synthesis (percent inhibition) was significantly less using LDL from the normocholesterolaemic diabetic patients or hypercholesterolaemic non-diabetic or diabetic patients compared with LDL from the normocholesterolaemic non-diabetic control subjects (47.4 +/- 3.9%, 39.1 +/- 5.1% and 35.2 +/- 4.1% vs 59.5 +/- 1.2%, p less than 0.01). However, hypertriglyceridaemia had no effect on LDL suppression of cholesterol synthesis. We conclude that hypertriglyceridaemia alters LDL composition but the alteration is not associated with the ability of LDL to regulate cholesterol synthesis.     

Lipoprotein composition in NIDDM: effects of dietary oleic acid on the composition,oxidisability and function of low and high density lipoproteins

Summary Oxidation of low density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis and is related to the fatty acid composition which is altered in diabetes mellitus. This study examines the relationship between the fatty acid composition of LDL and high density lipoprotein (HDL) and lipoprotein oxidation. A group of nine non-insulin-dependent diabetic (NIDDM) patients were compared to seven healthy control subjects before and after a high monounsaturated diet. Lipoproteins were isolated and oxidisability was measured by conjugated diene formation and lipid peroxide analysis. Serum HDL cholesterol was significantly lower in the diabetic patients. LDL cholesteryl ester linoleic acid in the diabetic patients was significantly higher at baseline and decreased after diet (p<0.05) while oleic acid increased in both diabetic and non-diabetic subjects (p<0.05). HDL cholesteryl ester oleic acid was lower in the diabetic patients compared with control subjects (p<0.05) before diet and it increased significantly after diet (p<0.05). LDL lipid peroxides and conjugated diene formation were related to LDL glycation (r=0.46, p<0.05 and r=0.49, p<0.05, respectively). Both decreased following diet (lipid peroxides for diabetic patients from 476±30 to 390±20 nmol/mg protein p<0.05 and for control subjects from 350±36 to 198±30 nmol/mg protein p<0.05). HDL conjugated diene formation decreased in both groups after diet but only significantly in the control group (55.4±7.5 to 53.2±6.7 nmol/mg protein for diabetic patients and 45.8±6.4 to 31.6±4.8 nmol/mg protein p<0.05 for control subjects). There was a positive correlation between LDL lipid peroxide formation and percentage of cholesteryl ester linoleic acid in LDL from diabetic patients (r=0.61, p<0.05) and control subjects (r=0.91, p<0.01). Fatty acid composition of LDL was reflected in the composition of HDL. In the presence of HDL lipoprotein peroxidation decreased. This decrease in lipoprotein peroxidation was positively related to the percentage of linoleic acid in LDL (r=0.71, p<0.05). This study confirms the close relationship between the fatty acid composition of LDL and HDL and demonstrates the importance of the fatty acid composition of the cholesteryl ester fraction in relation to LDL oxidation in diabetes. Linoleic acid in HDL appears to be a protecting factor against oxidation.Abbreviations BHT Butylated hydroxytoluene - EDTA ethyl-enediaminetetraacetic acid - TBARS thiobarbituric reacting substances - HPLC high performance liquid chromatography - MDA malondialdehyde - HbA_1c glycated haemoglobin     

Serum lipids and lipoproteins in insulin-dependent diabetic patients with persistent microalbuminuria

Serum lipid and lipoprotein concentrations were measured in 18 insulin-dependent diabetic patients with persistent microalbuminuria and an equal number with persistently normal albumin excretion. The groups were matched for sex, age, duration of diabetes, body mass index, insulin dose, and glycosylated haemoglobin. Diabetic patients with persistent microalbuminuria were found to have a significantly lower high density lipoprotein (HDL) cholesterol concentration (difference 0.29, 95% Cl 0.12 to 0.46, mmol l-1, p less than 0.01) and a higher low density lipoprotein (LDL) cholesterol:HDL cholesterol ratio (difference 0.97, 95% Cl 0.29 to 1.65, p less than 0.01) than patients with normal albumin excretion. No significant differences were found in total cholesterol, triglycerides, LDL cholesterol, apolipoprotein (apo) A-I and apo B concentrations. Compared to an age and sex-matched group of non-diabetic subjects with normal albumin excretion, diabetic patients with persistent microalbuminuria had significantly higher concentrations of total cholesterol (p less than 0.05), LDL cholesterol (p less than 0.05) and apo B (p less than 0.01), but a lower concentration of HDL cholesterol (p less than 0.05). No significant differences were found in serum lipids and lipoproteins between diabetic patients with normal albumin excretion and non-diabetic subjects.     

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Summary Cholesterol absorption and metabolism and LDL and HDL kinetics were investigated in 11 hypercholesterolaemic non-insulin-dependent diabetic men off and on a hypolipidaemic treatment with sitostanol ester, (3 g sitostanol daily) dissolved in rapeseed oil margarine, by a double-blind crossover study design. Serum total, VLDL and LDL cholesterol and apoprotein B fell significantly by 6±2, 12±6, 9±3 and 6±2%, mean ±SEM, and HDL cholesterol was increased by 11±4% (p<0.05) by sitostanol ester. LDL cholesterol and apoprotein B were significantly decreased in the dense (1.037–1.055 g/ml), but not light, LDL subfraction due to a significantly diminished transport rate for LDL apoprotein B, while the fractional catabolic rate was unchanged. HDL kinetics, measured with autologous apoprotein AI, was unaffected by sitostanol ester. Cholesterol absorption efficiency was markedly reduced from 25±2 to 9±2% (p<0.001) during sitostanol ester followed by proportionately decreased serum plant sterol proportions. Cholesterol precursor sterol proportions in serum, fecal neutral sterol excretion, and cholesterol synthesis, cholesterol transport, and biliary secretion were all significantly increased by sitostanol ester. We conclude that the sitostanol ester-induced decrease in cholesterol absorption compensatorily stimulated cholesterol synthesis, had no effect on fractional catabolic rate, but decreased transport rate for LDL apoprotein B so that serum total, VLDL and LDL cholesterol levels were decreased. Dietary rapeseed oil margarine rich in sitostanol ester was well tolerated, appears to be safe from the nutritional point of view and effective for lowering VLDL and LDL cholesterol and increasing HDL cholesterol in hypercholesterolaemic non-insulin-dependent diabetic subjects.Abbreviations Apo apoprotein - NIDDM non-insulin-dependent diabetes mellitus - VLDL very low density lipoprotein - IDL intermediate density lipoprotein - LDL low density lipoprotein - HDL high density lipoprotein - FCR fractional catabolic rate - TR transport rate Presented in part at the 65th Scientific Sessions of the American Heart Association, New Orleans, November 1992 (Circulation 1992; 86[Suppl I]: I-404)     

Serum lipoprotein(a) concentrations and apolipoprotein(a) phenotypes in the families of NIDDM patients

Summary We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotype in 87 members (42 males, 45 females) of 20 diabetic families, 26 of whom were diagnosed with non-insulin-dependent diabetes mellitus (NIDDM) with moderate glycaemic control (HbA_1c7.1±1.2%). Apo(a) phenotyping was performed by a sensitive, high-resolution technique using SDS-agarose/gradient PAGE (3–6%). To date, 26 different apo(a) phenotypes, including a null type, have been identified. Serum Lp(a) levels of NIDDM patients and non-diabetic members of the same family who had the same apo(a) phenotypes were compared, while case control subjects were chosen from high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups with the same apo(a) phenotypes in the same family. Serum Lp(a) levels were significantly higher in NIDDM patients than in non-diabetic subjects (39.8±33.3 vs 22.3±19.5 mg/dl, p<0.05). The difference in the mean Lp(a) level between the diabetic and non-diabetic groups was significantly (p<0.05) greater than that between the high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups. An analysis of covariance and a least square means comparison indicated that the regression line between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in the diabetic patient group was significantly (p<0.01) elevated for each apo(a) phenotype, compared to the regression line of the control group. These data, together with our previous findings that serum Lp(a) levels are genetically controlled by apo(a) phenotypes, suggest that Lp(a) levels in diabetic patients are not regulated by smaller apo(a) isoforms, and that serum Lp(a) levels are greater in diabetic patients than in non-diabetic family members, even when they share the same apo(a) phenotypes.Abbreviations Lp(a) Lipoprotein(a) - apo(a) apolipoprotein(a) - NIDDM non-insulin-dependent diabetes mellitus - TC total cholesterol - LDL low density lipoprotein - TG triglycerides - HDL-C high density lipoprotein-cholesterol - LDL-C low density lipoprotein-cholesterol - PBS phosphate buffered saline The first two authors contributed equally to this work     

Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment

Aim/hypothesis Cellular cholesterol efflux to plasma is important in reverse cholesterol transport and may be affected by simvastatin in type 1 diabetes mellitus.Methods In 14 moderately hypercholesterolaemic type 1 diabetic and 13 healthy men we determined plasma (apo)lipoproteins, pre- HDL formation, cholesteryl ester transfer protein (CETP) activity, phospholipid transfer protein (PLTP) activity, cholesterol esterification, cholesteryl ester transfer and the capacity of plasma to induce cholesterol efflux out of Fu5AH cells and fibroblasts. After diet run-in, diabetic patients were randomly treated with simvastatin 10, 20, 40 mg and placebo, once daily each, for 6 weeks in a double-blind crossover design.Results Plasma very low density lipid protein (VLDL)+LDL cholesterol, LDL cholesterol, HDL phospholipids, apolipoprotein (apo) A-I, apo B, CETP activity, PLTP activity, cholesterol esterification, cholesteryl ester transfer and the capacity of plasma to induce cholesterol efflux from Fu5AH cells and fibroblasts were higher in diabetic patients. Pre- HDL formation was unaltered. Simvastatin treatment decreased VLDL+LDL cholesterol, LDL cholesterol, triglycerides and apo B, CETP activity, cholesterol esterification and cholesteryl ester transfer. HDL cholesterol increased and its change was correlated with the change in cholesteryl ester transfer. The ability to promote cholesterol efflux from Fu5AH cells and fibroblasts did not change after simvastatin.Conclusions/interpretation The capacity of plasma from moderately hypercholesterolaemic type 1 diabetic patients to induce cholesterol efflux out of Fu5AH cells and fibroblasts is enhanced, probably due to higher apo A-I, HDL phospholipids and PLTP activity. Simvastatin increases HDL cholesterol in type 1 diabetic patients via lowering of plasma cholesteryl ester transfer. The HDL changes after simvastatin do not increase cellular cholesterol efflux further.